Energy metabolism ketone bodies

Several carrier systems have been shown to be present in the brain endothelium, allowing for the selective transport of a group of common substrates (Table 13.1). The most common system is the one that mediates the transport of glucose, which provides the brain with virtually all its energy. Carrier-mediated mechanisms are also responsible for the absorption of two other energy sources ketone bodies, which are derived from lipids, and lactic acid, a by-product of sugar metabolism. Carrier-mediated transport systems are also involved in the uptake of amino acids by the brain. The brain can manufacture its own small neutral and acidic amino acids however, large neutral and basic amino acids are obtained from the bloodstream. 

Acetyl-CoA is an "activated" two carbon compound found in many central metabolic pathways, including the citric acid cycle, the glyoxylate cycle, fatty acid synthesis, fatty acid oxidation, isoprene metabolism, amino sugar metabolism, ketone body metabolism, and cholesterol biosynthesis. The term "activated" used to describe the compound comes partly from the nature of the high energy... 

The liver is the only organ that can produce ketone bodies, yet it is one of the few that cannot use these molecules for energy production. Ketone bodies are produced when the rate of glucose synthesis is limited (i.e., substrates for gluconeogenesis are limited), and fatty acid oxidation is occurring rapidly. Ketone bodies can cross the blood-brain barrier and become a major fuel for the nervous system under conditions of starvation. Ketone body synthesis and metabolism have been described in Chapter 23. 

Ketosis has been considered to improve hypoxic tolerance by improving the metabolic energy state as a result of imbalance in glucose metabolism and energy insufficiency. Ketone bodies are suggested to have beneficial applications in both mitochondrial energy metabolism as well as non-oxidative metabolism. 

FIGURE 24.29 Reconversion of ketone bodies to acetyl-CoA in the mitochondria of many tissues (other than liver) provides significant metabolic energy. 

With increasing metabolism of fat through p oxidation, much of the mitochondrial CoA pool may become tied up as acyl- or acetyl-CoA. In such cases, the supply of free CoA can be diminished, and this may limit the rate of p oxidation. Upon prolonged fasting and heavy reliance on fat for energy, the liver induces the enzymes required for the formation of ketone bodies and brain induces enzymes required for their metabolism. 

Because glucose is the preferred fuel for the brain, an individual who experiences a rapid fall in glucose concentration leading to acute neuroglycopenia will initially feel confusion and may progress to coma and even death. In the event that the person survives 3-4 days, the brain can adapt its metabolism to utilize ketone bodies, metabolically derived from acetyl-CoA (see Figure 6.17), as a source of energy. 

During periods of fasting, muscles may also derive energy from the metabolism of ketone bodies (3-hydroxybutyrate and acetoacetate). These intermediates are... 

After removal of the a-amino group from the amino acids, the remainii ketoadds may be metabolized for energy or used for hepatic synthesis of glucose or ketone bodies. Table 1-17-3 shows this classification. 

The ketone bodies are released by the liver into the blood, in which they are easily soluble. Blood levels of ketone bodies therefore rise during periods of hunger. Together with free fatty acids, 3-hydroxybutyrate and acetoacetate are then the most important energy suppliers in many tissues (including heart muscle). Acetone cannot be metabolized and is exhaled via the lungs or excreted with urine. 

To channel ketone bodies into the energy metabolism, acetoacetate is converted with the help of succinyl CoA into succinic acid and acetoacetyl CoA, which is broken down by p-oxidation into acetyl CoA (not shown see p. 180). 

During periods of hunger, muscle proteins serve as an energy reserve for the body. They are broken down into amino acids, which are transported to the liver. In the liver, the carbon skeletons of the amino acids are converted into intermediates in the tricarboxylic acid cycle or into acetoacetyl-CoA (see p. 175). These amphibolic metabolites are then available to the energy metabolism and for gluconeogenesis. After prolonged starvation, the brain switches to using ketone bodies in order to save muscle protein (see p. 356). 

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